Substantial advances were made in the development of human T--T hybridomas which secrete a variety of immunoregulatory factors. These hybrids were established by the fusion of human blood T cells and a hypoxanthine/aminopterin/thymidine (HAT)-sensitive human T cell leukemia line. We developed the first human T--T cell hybridoma which secreted monoclonal B cell growth factors (BCGF) devoid of T cell growth factor (TCGF) or B cell differentiation factor (BCDF) thus providing a source of purified factor for the continuous growth of human B cell lines as well as a source of factor to dissect out the distinct phases of the B cell cycle of activation, proliferation, and differentiation. In this regard, we most recently developed hybrids which elaborated BCDF devoid of TCGF activity. These cloned hybrids lines were used to precisely characterize the nature of the growth factors and to initiate studies aimed at defining the nature of the growth factor receptors on the target cells in question. Such studies were previously not feasible with the crude factor-containing supernatants derived from cultures of heterogenous mononuclear cells. Model systems of human B cell hybridomas which had originally been developed in this laboratory were perfected with regard to the delineation of the precise conditions for optimizing the yield of antigen-specific B cell hybrids from the peripheral blood of immunized subjects. Improved methodologies for the cloning of antigen-specific human T cells from peripheral blood were developed and resulted in the production of T cell clones which were antigen specific, were MHC restricted with regard to DR or MB antigen-bearing presenting cells, and expressed functional helper activity. Furthermore, certain of these antigen-specific T cell clones were shown to secrete a variety of immunoregulatory T cell factors such as interleukin 2, gamma interferon, BCGF and BCDF.